Chemical toxicants affect our body function by interfering with our normal physiology, diethylstilbestrol (DES) represents a class of estrogenic compounds that had devastating effects on the well-being of these second generation. It was formerly in pregnant women and their fetuses were exposed to DES from 1947 to 1971 resulting in a spectrum of developmental abnormalities in both the female and the male reproductive tracts including cancer. The mode of DES action has recently been suggested to involve the repression of several developmentally important genes including Hox, Wnt, insulin-3 during critical developmental periods. Our long term goal is to study the genic pathway controlling reproductive tract development and how exogenous factors can influence the process. In this application we first propose to use the state of the art Affymetrix gene-array technology to encourage genes whose expression is altered by DES. Second, we will examine whether any of these candidate genes functions downstream of Hoxa10 and Hoxa11, as the function of these two genes in earlier reproductive tract development was revealed by knock-out mice. Information gathered from this study will be valuable both in the study of DES teratogenicity and normal uterine development.